Use of one or more shogaol(s) as an aphrodisiac

ABSTRACT

The present invention relates to the use of one or more shogaol(s) as aphrodisiacs. 
 
Advantageously, the shogaol(s) correspond(s) to the general formula I:  
                 
in which n is equal to 1, 2, 4, 6 or 8 and advantageously 1. The present invention also relates to a process for stimulating or arousing the libido in human beings, comprising the administration to a human being of an effective amount of one or more shogaol(s).

The present invention relates to aphrodisiacs. It relates in particularto the use of one or more shogaol(s) as aphrodisiacs.

Since the dawn of time, many substances have been used with the aim ofincreasing the sexual desire (the libido). Some of them have met withgreat success and have been handed down through the centuries. However,none of the substances has survived the meticulous scrutiny ofscientists. Consequently, the search for a genuine aphrodisiaccontinues.

The Applicant has found, surprisingly, that shogaol(s) has(have) anaphrodisiac action on men and women.

Shogaols have already been described as having deodorant and/orantiseptic activity (FR 2 758 086).

Certain shogaols are also known chemical constituents of plants of theAlpinia genus, such as Alpinia galanga or Alpinia officinarun orZingiber, such as Zingiber officinalis, Zingiber cassumunar or Zingiberzerumbet, obtained by extraction of their rhizome.

In particular, the ginger belonging to the Zingiber officinalis familyis a well-known spice used in many culinary preparations and has thereputation of being aphrodisiac. However, in view of the quantity ofchemical constituents present in its rhizome (geraniol, geranyl acetate,linalool, citronyl acetate, α-terpineol, borneol, bornyl acetate, neral,genarial, β-bisabolene, (−)-zingiberene, (+)-ar-curcumene,β-sesquiphellandrene, gingerols, etc.), it is difficult to know to whichof them this aphrodisiac activity is due. Furthermore, although theother pharmaceutical properties of ginger, such as its antiemeticaction, its action against travel sickness and its anti-inflammatoryaction, have been scientifically proven, this has never been so for itsaphrodisiac activity.

Similarly, although Alpinia galanga has also been considered in ancientIndian and Arabic manuscripts as having an aphrodisiac effect (IndianMateria Medica K. M., 1976, vol. 1, p. 79, Bombay Popular Prakashan Ed.;Notices et manuscrits de la Bibliothèque Nationale [Notices andManuscripts of the National Library], Volume 25, IBN EL BEITAR, p. 61,1883, Editions de l' Institut de France) has this effect, not proven todate, may be due to one of its many constituents other than shogaol.

The Applicant has thus discovered, surprisingly, that shogaol(s), (a)compound(s) of the arylalkanone family, has(have) an aphrodisiac actionon men and/or women.

The present invention thus relates to the use of one or more shogaol(s)as aphrodisiacs.

For the purposes of the present invention, the term “aphrodisiac” meansthe stimulation or arousal of the libido, i.e. the sexual desire.

Advantageously, the present invention relates to the use of one or moreshogaol(s) as erectogenic agents or to stimulate or arouse the libido inhumans.

Advantageously, the shogaol(s) correspond(s) to the general formula (I):

in which n is equal to 1, 2, 4, 6 or 8, and which are known,respectively, as [3]-shogaol, [4]-shogaol, [6]-shogaol, [8]-shogaol and[10]-shogaol. Even more advantageously, it is [3]-shogaol.

According to one particular embodiment, the shogaol(s) is(are) in theform of a crude extract of a plant of the Zingiberacea family,advantageously obtained by a process that comprises the following step:

-   a) preparation of a crude extract from fresh or dry rhizomes of the    said plant, by macerating a ground material of these rhizomes at a    temperature of between 10 and 35° C., followed by one or more    extractions at reflux of this ground material, or by subjecting a    ground material of the said rhizomes to a percolation at a    temperature of between 10 and 35° C., each of these operations    (maceration, extractions at reflux and percolation) being performed    by means of a suitable organic solvent or mixture of organic    solvents.

The maceration of the ground rhizome material, prior to its extraction,mainly has the effect of improving the placing in contact of the planttissues and of the solvent during the extraction. Its duration may bebetween about twelve hours and one week depending on the freshness ofthe rhizomes used.

For the maceration, extraction at reflux and percolation operations onthe ground material, water-miscible organic solvents with a relativelylow boiling point are advantageously used so as to be able subsequentlyto remove them easily by a simple evaporation, such as ethanol, methanolor acetone or mixtures thereof with water. However, since the shogaolsare soluble in many organic solvents, it is also possible to use otherorganic solvents, such as ethyl acetate, ethyl ether, chloroform ormethylene chloride.

In another particular embodiment, the shogaol(s) is(are) in the form ofa purified extract of a plant of the Zingiberacea family, advantageouslyobtained by a process that comprises, besides step a) described above,the following additional steps:

-   b) purification of the crude extract obtained in step a) by    subjecting the said extract, after removing the solvent(s) it    contains and taking it up in water, to one or more counter-current    extractions with a water-immiscible organic solvent or mixture of    organic solvents, and, if desired,-   c) chromatographic separation of the shogaols.

The water-immiscible organic solvent(s) that are useful for carrying outthe counter-current extractions of the crude extract in order to purifyit are those chosen especially from ethyl acetate, ethyl ether,chloroform and methylene chloride, and mixtures thereof.

Advantageously, the plant of the Zingiberacea family is chosen from thespecies alpinia galanga, alpinia officinarum, Zingiber officinalis,Zingiber cassumunar and Zingiber zerumbet, and even more advantageouslyit is Alpinia galanga.

For example, [3]-shogaol, [6]-shogaol and [8]-shogaol may be extractedfrom plants of the Alpinia genus such as Alpinia galanga or Alpiniaofficinarum, whereas [4]-shogaol and [10]-shogaol may be extracted fromplants of the Zingiber genus such as Zingiber officinalis, Zingibercassumunar or Zingiber zerumbet, in particular using the process asdescribed above.

Advantageously, the crude extract of Alpinia galanga contains an amountof [3]-shogaol of between, by weight, about 1 to 5% of the dry weight ofthe said extract. In accordance with the invention, this extract isobtained from fresh or dry rhizomes of the said plant.

Advantageously, the purified extract of Alpinia galanga contains anamount of [3]-shogaol at least equal by weight to 75% of the dry weightof the said extract.

The present invention also relates to the use of one or more shogaol(s)for the preparation of an aphrodisiac composition.

Advantageously, the aphrodisiac composition is formulated for an oraladministration, for example, in the form of powders, drinkable solutionsor suspensions, syrups, tablets or gel capsules.

The present invention also relates to a process for arousing orstimulating the libido in human beings, characterized in that itcomprises the administration to a human being of an effective amount ofone or more shogaol(s) as defined above.

The examples that follow for the preparation of extracts containingshogaols are given purely as illustrations of the subject of theinvention, of which they do not in any way constitute a limitation.

EXAMPLE 1 Preparation of a Crude Extract of Rhizomes of Alpinia galanga

One kilo of fresh rhizomes of Alpinia galanga is ground coarsely, takingcare not to overheat the ground portions. The water content of theground material thus obtained is determined, and it is left to maceratein 7 litres of ethanol, the titre of which is selected such that, giventhe water content of the ground material, the maceration solvent is 50%ethanol.

After macerating for 24 hours at about 20° C., the ground material isextracted at reflux with the maceration solvent for 30 minutes. Thissolvent is removed and replaced with an equal weight of 50% ethanol, andthe ground material is extracted again at reflux for 30 minutes. Theoperation is repeated once.

The 3 extracts obtained are combined (thus constituting a volume ofabout 19 litres), filtered on paper and then evaporated to dryness underreduced pressure.

A residue which weighs about 50 g is obtained, i.e. an approximate yieldof 30% relative to the dry weight of the rhizomes. This extract containsthe various shogaols present in the Alpinia galanga rhizomes([3]-shogaol, [6]-shogaol and [8]-shogaol) and its content of[3]-shogaol is generally between 1 and 5% (w/w) according to therhizomes used.

EXAMPLE 2 Preparation of a Purified Extract of Alpinia galanga Rhizomes

50 g of a crude extract, prepared in accordance with Example 1, aretaken up in 1 litre of distilled water and the mixture is boiled for 1minute with constant stirring. Stirring is continued until this extractis completely homogenized, and it is then cooled. It is then subjectedto 4 successive counter-current extractions each with 100 ml of ethylether.

The ether solutions are combined; anhydrous sodium sulphate is addedthereto to remove the water they contain; they are filtered throughpaper and evaporated to dryness under reduced pressure.

A residue that weighs 6.8 g is thus obtained, i.e. a yield of about 4%relative to the dry weight of the rhizomes. This extract, which mainlycontains [3]-shogaol, has a [3]-shogaol content that is generallygreater than 75% (w/w)

EXAMPLE 3 Production of [3]-shogaol

[3]-Shogaol may be obtained from Alpinia galanga rhizomes by preparing acrude extract of these rhizomes in accordance with Example 1, thenpurifying this extract in accordance with Example 2, and then subjectingthe extract thus purified to successive elutions on columns of silicagel, for example in the following manner.

10 g of a purified extract, prepared in accordance with Example 2, aresupplemented with 100 g of a silica gel G60 and 500 ml of chloroformwith constant stirring. As soon as the mixture is homogeneous, it isevaporated to dryness under reduced pressure so as to obtain a powder.

This powder is placed at the top of a column 10 cm in diameter and 50 cmlong, also containing silica gel G60 in petroleum ether. The column isfirst eluted with petroleum ether until the residue is less than 0.1%(about 10 litres of petroleum ether required to achieve this stage),then with 12 litres of benzene and finally with 8 litres of chloroform.

The chloroform phase is evaporated to dryness under reduced pressure,leaving a residue of about 2.3 g. This residue is then subjected to apreparative chromatography on a column 5 cm in diameter and 20 cm inlength, filled with C18 silica gel, and using a water/acetonitrilemixture (70/30) as elution gradient. The fraction containing the[3]-shogaol is eluted in a time of between 5 and 7 minutes for a flowrate of 30 ml/min.

The [3]-shogaol may be identified by high pressure liquid chromatography(HPLC) coupled to a mass spectrometer.

EXAMPLE 4 Preparation of an Aphrodisiac Composition in Oral Form

1 kilo of crude extract, prepared in accordance with Example 1, wasmixed intimately with 1 kilo of maltodextrin in a knife mill so as toensure better homogeneity of the mixture and to obtain a non-stickymobile powder. This powder was then distributed in No. 0 gel capsules soas to obtain a unit dose of 250 mg of crude extract.

Similarly, gel capsules may be manufactured using [3]-shogaol to obtaina unit dose of 25 mg of [3]-shogaol.

These crude or purified extracts or the shogaol(s) were testedsuccessfully in oral form as regards their aphrodisiac action on men andwomen.

1-7. (canceled)
 8. An aphrodisiac medicinal product, comprising at leastone shogaol.
 9. The product of claim 8, wherein the shogaol correspondsto the general formula (I):

in which n is equal to 1, 2, 4, 6 or
 8. 10. The product of claim 9,wherein n is equal to
 1. 11. The product of claim 8, wherein the shogaolis in the form of a crude extract of a plant of the Zingiberacea family.12. The product of claim 11, wherein the crude extract is obtained by aprocess comprising the following step: a) preparing the crude extractfrom fresh or dry rhizomes of the plant by macerating a ground materialof the rhizomes at a temperature of between 10 and 35° C., followed byextracting at least once the ground material at reflux, or by subjectingthe ground material of the rhizomes to a percolation at a temperature ofbetween 10 and 35° C., each of the maceration, extraction at reflux andpercolation operations being performed by means of an effective organicsolvent or a mixture of organic solvents.
 13. The product of claim 12,wherein the crude extract is obtained by a process comprising step a) asdefined in claim 12 and the following additional steps: b) purifying thecrude extract obtained in step a) by subjecting the extract, afterremoving the solvent it contains and taking it up in water, to at leastone counter-current extraction with a water-immiscible organic solventor mixture of water-immiscible organic solvents, and, optionally, c)chromatographically separating the shogaol.
 14. The product of claim 11,wherein the plant of the Zingiberacea family is the species Alpiniagalanga, Alpinia officinarum, Zingiber officinalis, Zingiber cassumunaror Zingiber zerumbet.
 15. The product of claim 14, wherein the plant ofthe Zingiberacea family is Alpinia galanga.
 16. The product of claim 8,wherein the product is an erectogenic medicinal product or a medicinalproduct for arousing or stimulating the libido in a human.
 17. Theproduct of claim 8, wherein the product is formulated for oraladministration.
 18. A process for arousing or stimulating the libido ina human, comprising administering to the human an effective amount of atleast one shogaol.
 19. The process of claim 18, wherein the arousal orstimulation of the libido is erectogenic.